Imaging of mammalian tissues has been used extensively to obtain information on the internal structures as well as on the biodistribution of molecules. This information can of course be utilized for diagnosis purposes. Several techniques based on different physical principles are currently available to obtain images that encompass a broad range of spatio-temporal resolution. Such techniques include Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), single-photon emission computed tomography (SPECT), X-ray, ultrasound and, now emerging, optical imaging.
In optical imaging three approaches have been used to generate the optical data necessary to reconstruct images of volume of interest (VOI) namely Continuous Wave (CW), which involves the measurement of light attenuation; Time Domain (TD), which involves injecting a pulse of light of short duration within the VOI and detecting the light as a function of time as it exits the VOI; and Frequency Domain (FD), which relies on frequency modulation of the light source and analysis of the phase and amplitude of the signal as it exits the VOI.
Continuous wave permits rapid acquisition and is the least expensive of the three approaches but provides a limited amount of information. More specifically, in CW imaging, the scatter coefficient of the VOI must be an assumption in order to obtain absorption coefficient information. CW cannot determine absorption separately from scatter. TD provides more information. In TD, a short laser pulse is injected in the part of the mammal to be imaged and the distribution of the time of flight of the photon exiting the volume of interest is measured. The resulting signal is referred to as a temporal point spread function (TPSF) that can be used to calculate such characteristics as the mean time of flight of photons. In FD, the intensity of the source is modulated with high frequency. As a result, a photon density wave propagates in the tissue and the amplitude and phase shift of the wave relative to the incident wave is measured. In principle, by scanning the tissue with a range of different frequencies, the entire TPSF can be reconstructed. However, in practice, a single frequency is usually employed to estimate the mean time of flight of the photons.
Image reconstruction using optical data belongs to the class of inverse problems. The problem consists of finding the distribution of optical parameters in tissue based on the detected optical signal. While image reconstruction techniques are still the subject of intense research activities, several tested approaches have been used with relative success. Some of these approaches are summarized and described in Boas et al. (IEEE SiG. Proc. Mag., Vol. 18, No. 6, pp. 57-75, 2001) and Hawrysz and Sevick-Muraca (Neoplasia, Vol. 2, No. 5, pp 388-417, 2000).
TD measurements provide detailed information about the absorption and the scatter from within a tissue, however, the method suffers from long acquisition time, expensive hardware and complicated software analysis. Furthermore the acquisition often results in noisy TPSF data from which accurate estimates of spatial optical information are difficult to obtain.
It would therefore be desirable to provide a method that would overcome the limitations of CW and TD, while retaining their advantages.